tbuckley/cabot-search huggingface dataset:
Bioactive Nonthermal Biocompatible Plasma Enhances Migration on Human Gingival Fibroblasts
Authors: Ihn Han, In‐Seok Song, Seung Ah Choi, Taebok Lee, Maksudbek Yusupov, Priyanka Shaw, Annemie Bogaerts, Eun Ha Choi, Jae Jun Ryu
Journal: Advanced Healthcare Materials (2022)

Abstract This study hypothesizes that the application of low‐dose nonthermal biocompatible dielectric barrier discharge plasma (DBD‐NBP) to human gingival fibroblasts (HGFs) will inhibit colony formation but not cell death and induce matrix metalloproteinase (MMP) expression, extracellular matrix (ECM) degradation, and subsequent cell migration, which can result in enhanced wound healing. HGFs treated with plasma for 3 min migrate to each other across the gap faster than those in the control and 5‐min treatment groups on days 1 and 3. The plasma‐treated HGFs show significantly high expression levels of the cell cycle arrest‐related p21 gene and enhanced MMP activity. Focal adhesion kinase (FAK) mediated attenuation of wound healing or actin cytoskeleton rearrangement, and plasma‐mediated reversal of this attenuation support the migratory effect of DBD‐NBP. Further, this work performs computer simulations to investigate the effect of oxidation on the stability and conformation of the catalytic kinase domain (KD) of FAK. It is found that the oxidation of highly reactive amino acids (AAs) Cys427, Met442, Cys559, Met571, Met617, and Met643 changes the conformation and increases the structural flexibility of the FAK protein and thus modulates its function and activity. Low‐dose DBD‐NBP‐induces host cell cycle arrest, ECM breakdown, and subsequent migration, thus contributing to the enhanced wound healing process.
Effect of acoustic cluster therapy (ACT®) combined with chemotherapy in a patient-derived xenograft mouse model of pancreatic cancer
Authors: Serina Ng, Andrew John Healey, Per Christian Sontum, Svein Kvåle, Sverre H. Torp, Einar Sulheim, Daniel Von Hoff, Haiyong Han
Journal: Journal of Controlled Release (2022)

Pancreatic ductal adenocarcinomas respond poorly to chemotherapy, in part due to the dense tumor stroma that hinders drug delivery. Ultrasound (US) in combination with microbubbles has previously shown promise as a means to improve drug delivery, and the therapeutic efficacy of ultrasound-mediated drug delivery is currently being evaluated in multiple clinical trials. However, most of these utilize echogenic contrast agents engineered for imaging, which might not be optimal compared to specialized formulations tailored for drug delivery. In this study, we evaluated the in vivo efficacy of phase-shifting microbubble-microdroplet clusters that, upon insonation, form bubbles in the size range of 20-30 μm. We developed a patient-derived xenograft model of pancreatic cancer implanted in mice that largely retained the stromal content of the originating tumor and compared tumor growth in mice given chemotherapeutics (nab-paclitaxel plus gemcitabine or liposomal irinotecan) with mice given the same chemotherapeutics in addition to ultrasound and acoustic cluster therapy. We found that acoustic cluster therapy significantly improved the effect of both chemotherapeutic regimens and resulted in 7.2 times higher odds of complete remission of the tumor compared to the chemotherapeutics alone.
Social Jet Lag, Weekend Warriors, and Physical Activity Patterns
Authors: Tianrui Luo, Yuqiang Liu, Maojin Yao
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
An Enhancer Demethylator Phenotype Converged to Immune Dysfunction and Resistance to Immune Checkpoint Inhibitors in Clear-Cell Renal Cell Carcinomas
Authors: Xiaofan Lu, Yann Vano, Alexandra Helleux, Xiaoping Su, Véronique Lindner, Guillaume Davidson, Roger Mouawad, Jean-Philippe Spano, Morgan Rouprêt, Reza Elaidi, Eva Compérat, Virginie Verkarre, Chengming Sun, Christine Chevreau, Mostefa Bennamoun, Hervé Lang, Thibault Tricard, Wenxuan Cheng, Li Xu, Irwin Davidson, Fangrong Yan, Wolf Herman Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G. Malouf
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of patients with clear-cell renal cell carcinomas (ccRCC). Although analyses of transcriptome, genetic alterations, and the tumor microenvironment (TME) have shed light into mechanisms of response and resistance to these agents, the role of epigenetic alterations in this process remains fully unknown. Experimental Design: We investigated the methylome of six ccRCC cohorts as well as one cell line dataset. Of note, we took advantage of the BIONIKK trial aiming to tailor treatments according to Paris Descartes 4-gene expression subgroups, and performed Illumina EPIC profiling for 46 samples related to patients treated with ipilimumab plus nivolumab, and 17 samples related to patients treated with sunitinib. Results: A group of tumors associated with enhancer demethylation was discovered, namely TED. TED was associated with tumors with sarcomatoid differentiation and poor clinical outcome. TED harbored TET1 promoter demethylation, activated the gene expression signature of epithelial–mesenchymal transition and IL6/JAK/STAT3 pathways, and displayed a TME characterized by both immune activation and suppressive populations, fibroblast infiltration, and endothelial depletion. In addition, TED was a predictive factor of resistance to the combination of first-line ipilimumab-nivolumab in the BIONIKK clinical trial. Finally, TED was associated with activation of specific regulons, which we also found to be predictive of resistance to immunotherapy in an independent cohort. Conclusions: We report on the discovery of a novel epigenetic phenotype associated with resistance to ICIs that may pave the way to better personalizing patients’ treatments. See related commentary by Zhou and Kim, p. 1170
Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation
Authors: Queralt Serra-Camprubí, Helena Verdaguer, Winona Oliveros, Núria Lupión-Garcia, Alba Llop-Guevara, Cristina Molina, Maria Vila-Casadesús, Anthony Turpin, Cindy Neuzillet, Joan Frigola, Jessica Querol, Mariana Yáñez-Bartolomé, Florian Castet, Carles Fabregat-Franco, Carmen Escudero-Iriarte, Marta Escorihuela, Enrique J. Arenas, Cristina Bernadó-Morales, Noemí Haro, Francis J. Giles, Óscar J. Pozo, Josep M. Miquel, Paolo G. Nuciforo, Ana Vivancos, Marta Melé, Violeta Serra, Joaquín Arribas, Josep Tabernero, Sandra Peiró, Teresa Macarulla, Tian V. Tian
Journal: Clinical Cancer Research (2022)

Cholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30%-50% of patients with CCA. Several types of tumor cells harboring these mutations exhibit homologous recombination deficiency (HRD) phenotype with enhanced sensitivity to PARP inhibitors (PARPi). However, PARPi treatment has not yet been tested for effectiveness in patient-derived models of advanced CCA.We have established a collection of patient-derived xenografts from patients with unresectable metastatic CCA (CCA_PDX). The CCA_PDXs were characterized at both histopathologic and genomic levels. We optimized a protocol to generate CCA tumoroids from CCA_PDXs. We tested the effects of PARPis in both CCA tumoroids and CCA_PDXs. Finally, we used the RAD51 assay to evaluate the HRD status of CCA tissues.This collection of CCA_PDXs recapitulates the histopathologic and molecular features of their original tumors. PARPi treatments inhibited the growth of CCA tumoroids and CCA_PDXs with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1. In line with these findings, only CCA_PDX and CCA patient biopsy samples with mutations of BRCA2 showed RAD51 scores compatible with HRD.Our results suggest that patients with advanced CCA with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA_PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials.
Social Jet Lag, Weekend Warriors, and Physical Activity Patterns
Authors: Wenming Shi
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Social Jet Lag, Weekend Warriors, and Physical Activity Patterns—Reply
Authors: Leandro F. M. Rezende, Yafeng Wang, Gerson Ferrari
Journal: JAMA Internal Medicine (2022)

In Reply We appreciate the letters to the editor from Dr Luo and colleagues and Dr Shi regarding methodologic issues in our study on the association of patterns of leisure-time physical activity (LTPA) with mortality.1 We provide some responses and explanations.
A Phase‐Change Mediated Intelligent Nanoplatform for Chemo/Photothermal/Photodynamic Therapy of Cancer
Authors: Xiaochun Hu, Hui Li, Ruihao Li, Sufeng Qiang, Mengyao Chen, Shuo Shi, Chunyan Dong
Journal: Advanced Healthcare Materials (2022)

Abstract Up to now, chemotherapy is still the main strategy for cancer treatment. However, the emergence of chemo‐resistance and systemic side effects often seriously affects the treatment and prognosis. Herein, an intelligent nanoplatform based on dendritic mesoporous organosilica nanoparticles (DMON) is constructed. The encapsulated phase‐change material, 1‐tetradecanol (TD) can serve as a “doorkeeper” and enable the responsive release of drugs based on the temperature changes. Meanwhile, polyethylene glycol (PEG) is used to improve the dispersibility and biocompatibility. Cisplatin is chosen as the model of chemotherapy drug, which is co‐loaded with indocyanine green (ICG) in DMON to produce DMON‐PEG‐cisplatin/ICG‐TD (DPCIT). Exciting, the hyperthermia and reactive oxygen species induced by ICG under the NIR‐laser irradiation will initiate a phase transition of TD to release cisplatin, thus leading a combined therapy (chemo/photothermal/photodynamic therapy). The results indicated that under laser irradiation, DPCIT can kill cancer cells and inhibit tumor growth efficiently. In addition, the designed nanoplatform reveals minimal systemic toxicity in vivo, in contrast, the distinct liver damage can be observed by the direct treatment of cisplatin. Overall, this research may provide a general approach for the targeted delivery and controlled release of chemotherapy drugs to realize a cooperatively enhanced multimodal tumor therapy.
The Philips Respironics Recall of Ventilators and Positive Airway Pressure Machines—Breakdowns in Medical Device Surveillance
Authors: Kushal T. Kadakia, Joseph S. Ross, Vinay K. Rathi
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
OncoLoop: A Network-Based Precision Cancer Medicine Framework
Authors: Alessandro Vasciaveo, Juan Martín Arriaga, Francisca Nunes de Almeida, Min Zou, Eugene F. Douglass, Florencia Picech, Maho Shibata, Antonio Rodriguez-Calero, Simone de Brot, Antonina Mitrofanova, Chee Wai Chua, Charles Karan, Ronald Realubit, Sergey Pampou, Jaime Y. Kim, Stephanie N. Afari, Timur Mukhammadov, Luca Zanella, Eva Corey, Mariano J. Alvarez, Mark A. Rubin, Michael M. Shen, Andrea Califano, Cory Abate-Shen
Journal: Cancer Discovery (2022)

Abstract Prioritizing treatments for individual patients with cancer remains challenging, and performing coclinical studies using patient-derived models in real time is often unfeasible. To circumvent these challenges, we introduce OncoLoop, a precision medicine framework that predicts drug sensitivity in human tumors and their preexisting high-fidelity (cognate) model(s) by leveraging drug perturbation profiles. As a proof of concept, we applied OncoLoop to prostate cancer using genetically engineered mouse models (GEMM) that recapitulate a broad spectrum of disease states, including castration-resistant, metastatic, and neuroendocrine prostate cancer. Interrogation of human prostate cancer cohorts by Master Regulator (MR) conservation analysis revealed that most patients with advanced prostate cancer were represented by at least one cognate GEMM-derived tumor (GEMM-DT). Drugs predicted to invert MR activity in patients and their cognate GEMM-DTs were successfully validated in allograft, syngeneic, and patient-derived xenograft (PDX) models of tumors and metastasis. Furthermore, OncoLoop-predicted drugs enhanced the efficacy of clinically relevant drugs, namely, the PD-1 inhibitor nivolumab and the AR inhibitor enzalutamide. Significance: OncoLoop is a transcriptomic-based experimental and computational framework that can support rapid-turnaround coclinical studies to identify and validate drugs for individual patients, which can then be readily adapted to clinical practice. This framework should be applicable in many cancer contexts for which appropriate models and drug perturbation data are available. This article is highlighted in the In This Issue feature, p. 247
Equivalent Impact of Elevated Lipoprotein(a) and Familial Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease
Authors: Berit Storgaard Hedegaard, Christian Sørensen Bork, Morten Kaltoft, Ib Christian Klausen, Erik Berg Schmidt, Pia Rørbæk Kamstrup, Anne Langsted, Børge Grønne Nordestgaard
Journal: Journal of the American College of Cardiology (2022)
Outcomes of Pregnancy in Women With Bioprosthetic Heart Valves With or Without Valve Dysfunction
Authors: Barbara Wichert-Schmitt, Jasmine Grewal, A. Kinga Malinowski, Birgit Pfaller, Katie L. Losenno, Marla C. Kiess, Jack M. Colman, Wendy Tsang, Jennifer Mason, Samuel C. Siu, Candice K. Silversides
Journal: Journal of the American College of Cardiology (2022)
Randomized Trials of Percutaneous Microaxial Flow Pump Devices
Authors: Mohit Pahuja, Adam Johnson, Ryan Kabir, Sukhdeep Bhogal, Jason P. Wermers, Nelson L. Bernardo, Itsik Ben-Dor, Hayder Hashim, Lowell F. Satler, Farooq H. Sheikh, Ron Waksman
Journal: Journal of the American College of Cardiology (2022)
Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results
Authors: Paolo Ghia, Andrzej Pluta, Małgorzata Wach, Daniel Lysak, Martin Šimkovič, Iryna Kriachok, Árpád Illés, Javier de la Serna, Sean Dolan, Philip Campbell, Gerardo Musuraca, Abraham Jacob, Eric J. Avery, Jae Hoon Lee, Ganna Usenko, Min Hui Wang, Ting Yu, Wojciech Jurczak
Journal: HemaSphere (2022)

Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator's choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator's choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL.
Until programmed death do us tolerant
Authors: David W. Scott
Journal: Journal of Clinical Investigation (2022)

Hemophilia inhibitorsPatients with mutations in the F8 gene, encoding coagulation protein factor VIII (FVIII), have an X-linked bleeding disorder known as hemophilia A (HemA) and lack FVIII or functional FVIII protein (1, 2).These patients may suffer recurrent spontaneous bleeds or more serious trauma-induced bleeding crises and often experience substantial morbidity due to recurrent bleeding into the joints (3, 4).Standard treatment for HemA involves infusion of recombinant FVIII or plasma-derived FVIII on demand or prophylactically.However, up to 30% of treated patients develop antibodies that can block and inhibit the function of this life-saving therapy (4, 5) since they are not immunologically tolerant to this human protein.The antibodies that neutralize FVIII function, referred to as "inhibitors" (6), pose a major clinical challenge, as once formed, inhibitor titers are difficult to reduce or eliminate.In this issue of the JCI, Becker-Gotot, Meissner, and colleagues (7) examined inhibitor formation in a mouse model for HemA (HemA mice).HemA mice, which have FVIII deficiency via removal of coding exon 16, were developed by Bi et al. ( 8) and have been used by researchers in the field for decades.Notably, nearly 100% of these HemA mice develop inhibitors to intravenously administered FVIII, whereas approximately 30% of patients with severe HemA develop clinically relevant inhibitors.We know that the immune response to FVIII is highly T (helper) cell dependent ( 9), but it is regulated in FVIII-sufficient mice (and humans) by T regulatory cells (Tregs) (10).In previous studies, Gotot and colleagues provided evidence that the regulated immune response likely requires programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) interactions (11,12), which leads to Treg-dependent apoptosis in wild-type (WT) mice.
BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1
Authors: Lorric Delage, Mireille Lambert, Émilie Bardel, Cindy Kundlacz, Dimitri Chartoire, Axel Conchon, Anne-Laure Peugnet, Lucas Gorka, Patrick Auberger, Arnaud Jacquel, Carole Soussain, Olivier Destaing, Henri-Jacques Delecluse, Susanne Delecluse, Samir Merabet, Alexandra Traverse-Glehen, Gilles Salles, Emmanuel Bachy, Marc Billaud, Hervé Ghesquières, Laurent Genestier, Jean-Pierre Rouault, Pierre Sujobert
Journal: Blood (2022)
Letter by Lakshmanan et al Regarding Article “Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy”
Authors: Suvasini Lakshmanan, Matthew J. Budoff, John R. Nelson
Journal: Circulation (2022)